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Determination of Stromelysin-3 function in the Biology of normal and tumoral mammary gland through transgenic animal analyses

Objective

Breast carcinomas remain the first cause of death for women in European countries. One in ten women will develop a breast carcinoma in their life time, and moreover the incidence of the disease is continuously increasing. The fatal outcome of this carcinoma results from the lack of effective treatment of the disease at the metastatic step. Stromelysin-3, a putative metalloprotease, is thought to play a role in the invasive processes by which a primary tumor cell invades a secondary tissue in order to develop a metastasis.
The present research project involves both molecular and cellular biology, in order to better understand the physiological and pathological function of the stromelysin-3 gene in remodelling processes observed in breast tumor invasion and during apoptotic post-weaning involution of the mammary gland.
We have:
- established the various DNA constructs
- obtained transgenic animals heterozygoos for all of the constructs
- developed the assays necessary to analyse the transgenic animals
- studied the expression of ST3 during mouse development
- studied tumorigenicity of cell lines expressing or non-expressing ST3 in nude mice
The main results have been published in 1996, in the Journal of Clinical Investigation. In this paper, we demonstrate for the first time, that ST3 is involved, in vivo, in tumor processes. In fact, ST3 expression in MCF7 breast cancer cells promotes tumor take in nude mice, presumably by favoring cancer cell survival in a tissue environment initially not permissive for tumor growth.

Call for proposal

Data not available

Funding Scheme

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Coordinator

Institut de Génètique et de Biologie Moléculaire et Cellulaire (IGBMC)
Address

67400 Illkirch
France
 

Participants (4)

State University Hospital
Belgium
Address

Ghent
 
The Fibiger Institute of the Danish Cancer Society
Denmark
Address

Copenhagen
 
UC Dublin
Ireland
Address

Dublin
 
University of Cambridge
United Kingdom
Address
Trumpington Street
CB2 1PZ Cambridge